Is TNC p.Arg1891= (c.5673A>G) pathogenic?

TNC p.Arg1891= (c.5673A>G) is classified Benign in TNC (ClinVar, Multiple submitters, 3 submitters; last evaluated 2020-10-20). Common (popmax 28%, nfe) — too common for a highly-penetrant pathogenic allele.

TNC p.Arg1891=

Q: How common is TNC p.Arg1891= (c.5673A>G) in the general population?

TNC p.Arg1891= (c.5673A>G) is common (popmax 28%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.5673A>G · rs12347433 · VCV1182259

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 28%, nfe) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.297	indeterminate
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.5	GERP 1.7, phastCons 1
Overall
CADD	11.83	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 28% European (non-Finnish) · 330,273/1,178,958 alleles

Filtering AF 27.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 27.9%

Overall 25.3% 407,454/1,611,976 alleles · common exomes 376,242/1,459,858 · genomes 31,212/152,118 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	28%	4
Finnishnot grpmax-eligible	27.7%	4
Amishnot grpmax-eligible	24.9%	4
Remaining individualsnot grpmax-eligible	22.9%	4
Middle Eastern	20%	5
Admixed American	19.5%	5
South Asian	16.1%	6
Ashkenazi Jewishnot grpmax-eligible	15.6%	6
East Asian	14.4%	7
African / African-American	8.64%	12

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: TNC
Protein: p.Arg1891=
Coding: c.5673A>G
MANE Select: NM_002160
dbSNP: rs12347433
Type: single nucleotide variant
Location: chr9:115035318 (GRCh38)
Gene constraint: LOEUF 0.608 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.48 · 21 PDB
Residue 1891: the fibronectin type-iii 15 domain

Full TNC gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TNC p.Arg1891Lys Uncertain significance ★ ⚠ same residue
TNC p.Arg1127Trp Uncertain significance ★★ ⚠ same type
TNC p.Arg608Cys Uncertain significance ★★ ⚠ same type
TNC p.Arg669His Uncertain significance ★★ ⚠ same type
TNC p.Arg747Trp Uncertain significance ★★ ⚠ same type
TNC p.Asn507Lys Uncertain significance ★★ ⚠ same type
TNC p.Asp2059Glu Uncertain significance ★★ ⚠ same type
TNC p.Asp831Asn Uncertain significance ★★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/tnc-p-arg1891 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown